Title : Mechanisms of
cholinesterase inhibition by inorganic mercury
Abstract :
- The poorly known mechanism of inhibition of cholinesterases by inorganic mercury (HgCl2) has been studied with a view to using these enzymes as biomarkers or as biological components of biosensors to survey polluted areas
- The inhibition of a variety of cholinesterases by HgCl2 was investigated by kinetic studies, X-ray crystallography, and dynamic light scattering
- Our results show that when a free sensitive sulfhydryl group is present in the enzyme , as in Torpedo californica acetylcholinesterase , inhibition is irreversible and follows pseudo-first-order kinetics that are completed within 1 h in the micromolar range
- When the free sulfhydryl group is not sensitive to mercury (Drosophila melanogaster acetylcholinesterase and human butyrylcholinesterase ) or is otherwise absent (Electrophorus electricus acetylcholinesterase ), then inhibition occurs in the millimolar range
- Inhibition follows a slow binding model, with successive binding of two mercury ions to the enzyme surface
- Binding of mercury ions has several consequences: reversible inhibition, enzyme denaturation, and protein aggregation, protecting the enzyme from denaturation
- Mercury-induced inactivation of cholinesterases is thus a rather complex process
- Our results indicate that among the various cholinesterases that we have studied, only Torpedo californica acetylcholinesterase is suitable for mercury detection using biosensors, and that a careful study of cholinesterase inhibition in a species is a prerequisite before using it as a biomarker to survey mercury in the environment
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